The current landscape of exercise and female fertility research: a narrative review.

In brief: Females with obesity may experience infertility and can improve their fertility through exercise. This review found that most exercise interventions improve fertility outcomes regardless of technique, intensity, or duration. More detailed reporting through the lens of exercise prescription should be included in future studies. Abstract: Female infertility disproportionately affects people with obesity. Exercise often improves fertility outcomes for this population, however, there is limited prescriptive evidence. Specifically, there is a lack of information on the ideal type, frequency, intensity, and setting of exercise to improve fertility outcomes. Using principles of exercise prescription, this review aimed to describe the scope of exercise interventions that have been explored and fertility outcomes measured for people with female infertility and obesity. A search was completed in PubMed, Embase, Cochrane, and CINAHL, identifying 16 relevant published articles. Overall, exercise had a positive impact on female fertility outcomes in people with obesity, though there were large variations in the exercise interventions prescribed and outcomes measured. Cyclic exercise (i.e. walking and cycling) was the most common technique incorporated, though a combination of cyclic, acyclic (i.e. circuit training and boot camp), or individualization was often used. Several fertility outcomes were reported; however, the rate of conception, pregnancy, and live birth rates were the most common, which, we suggest, should always be reported in fertility intervention research. We stress that future studies provide more thorough descriptions of their implemented exercise interventions to facilitate reproducibility and comparisons between studies. Closer attention to the principles of exercise prescription when developing and reporting exercise interventions will help improve fertility outcomes, mainly live birth rates, for those with female infertility and obesity.

ARGUS: Visualization of AI-Assisted Task Guidance in AR.

The concept of augmented reality (AR) assistants has captured the human imagination for decades, becoming a staple of modern science fiction. To pursue this goal, it is necessary to develop artificial intelligence (AI)-based methods that simultaneously perceive the 3D environment, reason about physical tasks, and model the performer, all in real-time. Within this framework, a wide variety of sensors are needed to generate data across different modalities, such as audio, video, depth, speech, and time-of-flight. The required sensors are typically part of the AR headset, providing performer sensing and interaction through visual, audio, and haptic feedback. AI assistants not only record the performer as they perform activities, but also require machine learning (ML) models to understand and assist the performer as they interact with the physical world. Therefore, developing such assistants is a challenging task. We propose ARGUS, a visual analytics system to support the development of intelligent AR assistants. Our system was designed as part of a multi-year-long collaboration between visualization researchers and ML and AR experts. This co-design process has led to advances in the visualization of ML in AR. Our system allows for online visualization of object, action, and step detection as well as offline analysis of previously recorded AR sessions. It visualizes not only the multimodal sensor data streams but also the output of the ML models. This allows developers to gain insights into the performer activities as well as the ML models, helping them troubleshoot, improve, and fine-tune the components of the AR assistant.

High-fat diet increases electron transfer flavoprotein synthesis and lipid respiration in skeletal muscle during exercise training in female mice.

High-fat diet (HFD) and exercise remodel skeletal muscle mitochondria. The electron transfer flavoproteins (ETF) transfer reducing equivalents from ß-oxidation into the electron transfer system. Exercise may stimulate the synthesis of ETF proteins to increase lipid respiration. We determined mitochondrial remodeling for lipid respiration through ETF in the context of higher mitochondrial abundance/capacity seen in female mice. We hypothesized HFD would be a greater stimulus than exercise to remodel ETF and lipid pathways through increased protein synthesis alongside increased lipid respiration. Female C57BL/6J mice (n = 15 per group) consumed HFD or low-fat diet (LFD) for 4 weeks then remained sedentary (SED) or completed 8 weeks of treadmill training (EX). We determined mitochondrial lipid respiration, RNA abundance, individual protein synthesis, and abundance for ETFα, ETFß, and ETF dehydrogenase (ETFDH). HFD increased absolute and relative lipid respiration (p = 0.018 and p = 0.034) and RNA abundance for ETFα (p = 0.026), ETFß (p = 0.003), and ETFDH (p = 0.0003). HFD increased synthesis for ETFα and ETFDH (p = 0.0007 and p = 0.002). EX increased synthesis of ETFß and ETFDH (p = 0.008 and p = 0.006). Higher synthesis rates of ETF were not always reflected in greater protein abundance. Greater synthesis of ETF during HFD indicates mitochondrial remodeling which may contribute higher mitochondrial lipid respiration through enhanced ETF function.

Integrative rare disease biomedical profile based network supporting drug repurposing or repositioning, a case study of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most aggressive and common malignant primary brain tumor; however, treatment remains a significant challenge. This study aims to identify drug repurposing or repositioning candidates for GBM by developing an integrative rare disease profile network containing heterogeneous types of biomedical data. METHODS: We developed a Glioblastoma-based Biomedical Profile Network (GBPN) by extracting and integrating biomedical information pertinent to GBM-related diseases from the NCATS GARD Knowledge Graph (NGKG). We further clustered the GBPN based on modularity classes which resulted in multiple focused subgraphs, named mc_GBPN. We then identified high-influence nodes by performing network analysis over the mc_GBPN and validated those nodes that could be potential drug repurposing or repositioning candidates for GBM. RESULTS: We developed the GBPN with 1,466 nodes and 107,423 edges and consequently the mc_GBPN with forty-one modularity classes. A list of the ten most influential nodes were identified from the mc_GBPN. These notably include Riluzole, stem cell therapy, cannabidiol, and VK-0214, with proven evidence for treating GBM. CONCLUSION: Our GBM-targeted network analysis allowed us to effectively identify potential candidates for drug repurposing or repositioning. Further validation will be conducted by using other different types of biomedical and clinical data and biological experiments. The findings could lead to less invasive treatments for glioblastoma while significantly reducing research costs by shortening the drug development timeline. Furthermore, this workflow can be extended to other disease areas.

Integrative Rare Disease Biomedical Profile based Network Supporting Drug Repurposing, a case study of Glioblastoma.

Background Glioblastoma (GBM) is the most aggressive and common malignant primary brain tumor; however, treatment remains a significant challenge. This study aims to identify drug repurposing candidates for GBM by developing an integrative rare disease profile network containing heterogeneous types of biomedical data. Methods We developed a Glioblastoma-based Biomedical Profile Network (GBPN) by extracting and integrating biomedical information pertinent to GBM-related diseases from the NCATS GARD Knowledge Graph (NGKG). We further clustered the GBPN based on modularity classes which resulted in multiple focused subgraphs, named mc_GBPN. We then identified high-influence nodes by performing network analysis over the mc_GBPN and validated those nodes that could be potential drug repositioning candidates for GBM. Results We developed the GBPN with 1,466 nodes and 107,423 edges and consequently the mc_GBPN with forty-one modularity classes. A list of the ten most influential nodes were identified from the mc_GBPN. These notably include Riluzole, stem cell therapy, cannabidiol, and VK-0214, with proven evidence for treating GBM. Conclusion Our GBM-targeted network analysis allowed us to effectively identify potential candidates for drug repurposing. This could lead to less invasive treatments for glioblastoma while significantly reducing research costs by shortening the drug development timeline. Furthermore, this workflow can be extended to other disease areas.

Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans.

Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms during initial training adaptations. We used short-term high-intensity interval training (HIIT) to determine changes to mitochondrial respiration and regulatory pathways that occur early in remodeling. Fifteen normal-weight sedentary adults started seven sessions of HIIT over 14 days and 14 participants completed the intervention. We collected vastus lateralis biopsies before and 48 h after HIIT to determine mitochondrial respiration, RNA sequencing, and Western blotting for proteins of mitochondrial respiration and degradation via autophagy. HIIT increased respiration per mitochondrial protein for lipid (+23% P = 0.020), complex I (+18%, P = 0.0015), complex I + II (+14%, P < 0.0001), and complex II (+24% P < 0.0001). Transcripts that increased with HIIT identified several gene sets of mitochondrial respiration, particularly for complex I, whereas transcripts that decreased identified pathways of DNA and chromatin remodeling. HIIT lowered protein abundance of autophagy markers for p62 (-19%, P = 0.012) and LC3 II/I (-20%, P = 0.004) in whole tissue lysates but not isolated mitochondria. Meal tolerance testing revealed HIIT increased the change in whole body respiratory exchange ratio and lowered cumulative plasma insulin concentrations. Gene transcripts and respiratory function indicate remodeling of mitochondria within 2 wk of HIIT. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation.NEW & NOTEWORTHY Aerobic training stimulates mitochondrial metabolism in skeletal muscle that is linked to improvements to whole body fuel metabolism. The mechanisms driving changes to the quantity and quality (function per unit) of mitochondria are less known. We used seven sessions of high-intensity interval training (HIIT) to determine functional changes and mechanisms of mitochondrial remodeling in skeletal muscle. HIIT increased mitochondrial respiration per mass for fatty acids, complex I, and complex II substrates. HIIT-induced remodeling pathways including gene transcripts for mitochondrial respiration (via RNA sequencing of muscle tissue) and proteins related to complex I respiration. We conclude that an early feature of aerobic training is increased mitochondrial protein quality via improved respiration and induction of mitochondrial transcriptional patterns.

Impact of 4 weeks of western diet and aerobic exercise training on whole-body phenotype and skeletal muscle mitochondrial respiration in male and female mice.

High dietary fat intake induces significant whole-body and skeletal muscle adaptations in mice, including increased capacity for fat oxidation and mitochondrial biogenesis. The impact of a diet that is high in fat and simple sugars (i.e., western diet [WD]), particularly on regulation of skeletal muscle mitochondrial function, is less understood. The purpose of the current study was to determine physiologic adaptations in mitochondrial respiratory capacity in skeletal muscle during short-term consumption of WD, including if adaptive responses to WD-feeding are modified by concurrent exercise training or may be sex-specific. Male and female C57BL/6J mice were randomized to consume low-fat diet (LFD) or WD for 4 weeks, with some WD-fed mice also performing concurrent treadmill training (WD + Ex). Group sizes were n = 4-7. Whole-body metabolism was measured using in-cage assessment of food intake and energy expenditure, DXA body composition analysis and insulin tolerance testing. High-resolution respirometry of mitochondria isolated from quadriceps muscle was used to determine skeletal muscle mitochondrial respiratory function. Male mice fed WD gained mass (p < 0.001), due to increased fat mass (p < 0.001), and displayed greater respiratory capacity for both lipid and non-lipid substrates compared with LFD mice (p < 0.05). There was no effect of concurrent treadmill training on maximal respiration (WD + Ex vs. WD). Female mice had non-significant changes in body mass and composition as a function of the interventions, and no differences in skeletal muscle mitochondrial oxidative capacity. These findings indicate 4 weeks of WD feeding can increase skeletal muscle mitochondrial oxidative capacity among male mice; whereas WD, with or without exercise, had minimal impact on mass gain and skeletal muscle respiratory capacity among female mice. The translational relevance is that mitochondrial adaptation to increases in dietary fat intake that model WD may be related to differences in weight gain among male and female mice.

Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation.

Phagocytes migrate into tissues to combat infection and maintain tissue homeostasis. As dysregulated phagocyte migration and function can lead to inflammation or susceptibility to infection, identifying molecules that control these processes is critical. Here, we show that the tetraspanin CD82 restrains the migration of neutrophils and macrophages into tissues. Cd82 -/- phagocytes exhibited excessive migration during in vivo models of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasite L. mexicana. However, with the latter, while Cd82 -/- macrophages infiltrated infection sites at higher proportions, cutaneous L. mexicana lesions were larger and persisted, indicating a failure to control infection. Analyses of in vitro bone-marrow-derived macrophages showed CD82 deficiency altered cellular morphology, and impaired gene expression and metabolism in response to anti-inflammatory activation. Altogether, this work reveals an important role for CD82 in restraining phagocyte infiltration and mediating their differentiation in response to stimulatory cues.

A Physics-Informed Convolutional Neural Network with Custom Loss Functions for Porosity Prediction in Laser Metal Deposition.

Physics-informed machine learning is emerging through vast methodologies and in various applications. This paper discovers physics-based custom loss functions as an implementable solution to additive manufacturing (AM). Specifically, laser metal deposition (LMD) is an AM process where a laser beam melts deposited powder, and the dissolved particles fuse to produce metal components. Porosity, or small cavities that form in this printed structure, is generally considered one of the most destructive defects in metal AM. Traditionally, computer tomography scans measure porosity. While this is useful for understanding the nature of pore formation and its characteristics, purely physics-driven models lack real-time prediction ability. Meanwhile, a purely deep learning approach to porosity prediction leaves valuable physics knowledge behind. In this paper, a hybrid model that uses both empirical and simulated LMD data is created to show how various physics-informed loss functions impact the accuracy, precision, and recall of a baseline deep learning model for porosity prediction. In particular, some versions of the physics-informed model can improve the precision of the baseline deep learning-only model (albeit at the expense of overall accuracy).

Location-Based Sedentary Time and Physical Activity in People Living With Coronary Artery Disease.

PURPOSE: Sedentary time (ST) and lack of physical activity increase the risk of adverse outcomes for those living with coronary artery disease (CAD). Little is known about how much ST, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) that CAD participants not attending cardiac rehabilitation engage in, the locations where they engage in these behaviors, and how far from home the locations are. METHODS: Participants completed a survey and wore an accelerometer and global positioning system receiver for 7 d at baseline and 6 mo later. RESULTS: Accelerometer analyses (n = 318) showed that participants averaged 468.4 ± 102.7 of ST, 316.1 ± 86.5 of LPA, and 32.9 ± 28.9 of MVPA min/d at baseline. ST and LPA remained stable at 6 mo, whereas MVPA significantly declined. The global positioning system (GPS) analyses (n = 315) showed that most of participant ST, LPA, and MVPA time was spent at home followed by other residential, retail/hospitality, and work locations at baseline and 6 mo. When not at home, the average distance to a given location ranged from approximately 9 to 18 km. CONCLUSIONS: Participants with CAD spent the majority of their time being sedentary. Home was the location used the most to engage in ST, LPA, and MVPA. When not home, ST, LPA, and MVPA were distributed across a variety of locations. The average distance from home to a given location suggests that proximity to home may not be a barrier from an intervention perspective.

Understanding Men's Experiences With Prostate Cancer Stigma: A Qualitative Study.

PURPOSE: The purpose of this study was to explore the experiences and perspectives of men who have had prostate cancer to better understand the effect of prostate cancer and associated stigmas on men in the Canadian province Newfoundland and Labrador (NL). PARTICIPANTS & SETTING: Eleven men from NL who have had prostate cancer participated in semistructured interviews exploring their perspectives and experiences of prostate cancer and stigma. METHODOLOGIC APPROACH: A social-ecological framework was used to understand experiences from different domains. Interviews were analyzed using Lichtman's three Cs approach. Analysis focused on establishing themes of the participants' lived experience of prostate cancer and related stigma. FINDINGS: Participants described how emasculating a prostate cancer diagnosis can feel. They identified ways prostate cancer negatively affected their behaviors and sense of self, described coping with the diagnosis and different strategies, and talked about broader system change required to address prostate cancer stigma. Participants expressed a need for additional support from healthcare providers (HCPs). IMPLICATIONS FOR NURSING: HCPs, such as oncology nurses, may be able to reduce stigmatization by providing patient navigation, improving information delivery, or providing psychosocial counseling to individuals experiencing feelings of internal or external stigmatization related to prostate cancer.

A prospective randomized, double-blinded clinical study evaluating the efficacy and safety of bupivacaine versus morphine-bupivacaine in caudal epidurals in cats with urethral obstruction.

OBJECTIVE: To investigate the efficacy and safety of the caudal epidural technique in cats with urethral obstruction (UO). DESIGN: Prospective, double-blinded, randomized, sham-controlled study. ANIMALS: Eighty-eight male cats with UO. INTERVENTIONS: Thirty cats randomized to bupivacaine epidural (BUP), 28 cats to bupivacaine-morphine epidural (BUP/MOR), and 30 cats to sham epidural (SHAM). MEASUREMENTS AND MAIN RESULTS: Time to perform the epidural and efficacy of the epidural was assessed by evaluation of tail and perineal responses. The amount of propofol for urinary catheterization and time to administration of rescue analgesia (buprenorphine) was recorded. Cats were monitored for epidural complications. The median time to perform the epidural was 2 min (range, 0.2-13 min and range, 0.5-13 min), with an epidural success rate of 70%. The median amount of propofol administered for urinary catheterization was significantly less in the BUP (2.1 mg/kg; range, 0-7.5 mg/kg) and MOR/BUP cats (1.85 mg/kg; range, 0-8.6 mg/kg) as compared to SHAM cats (4 mg/kg; range, 0-12.7 mg/kg) (P = 0.006, P = 0.0008, respectively). The median time to administration of rescue analgesia was also significantly longer in the BUP (10 h; range, 2-32 h) and MOR/BUP cats (10 h; range, 4-45 h) as compared to SHAM cats (4 h; range, 2-36 h) (P = 0.0026, P = 0.0004, respectively). There were no recognized complications related to the epidural. CONCLUSION: Caudal epidural appears to be safe, may reduce the amount of IV anesthesia needed to facilitate urinary catheterization, and can be used to provide long-term analgesia in the hospital.

Cell Kinetics in the Adult Neurogenic Niche and Impact of Diet-Induced Accelerated Aging.

Neurogenesis in the adult brain, a powerful mechanism for neuronal plasticity and brain repair, is altered by aging and pathological conditions, including metabolic disorders. The search for mechanisms and therapeutic solutions to alter neurogenesis requires understanding of cell kinetics within neurogenic niches using a high-throughput quantitative approach. The challenge is in the dynamic nature of the process and multiple cell types involved, each having several potential modes of division or cell fate. Here we show that cell kinetics can be revealed through a combination of the BrdU/EdU pulse-chase, based on the circadian pattern of DNA replication, and a differential equations model that describes time-dependent cell densities. The model is validated through the analysis of cell kinetics in the cerebellar neurogenic niche of normal young adult male zebrafish, with cells quantified in 2D (sections), and with neuronal fate and reactivation of stem cells confirmed in 3D whole-brain images (CLARITY). We then reveal complex alterations in cell kinetics associated with accelerated aging due to chronic high caloric intake. Low activity of neuronal stem cells in this condition persists 2 months after reverting to normal diet, and is accompanied by overproduction of transient amplifying cells, their accelerated cell death, and slow migration of postmitotic progeny. This combined experimental and mathematical approach should allow for relatively high-throughput analysis of early signs of pathological and age-related changes in neurogenesis, evaluation of specific therapeutic targets, and drug efficacy.SIGNIFICANCE STATEMENT Understanding normal cell kinetics of adult neurogenesis and the type of cells affected by a pathological process is needed to develop effective prophylactic and therapeutic measures directed at specific cell targets. Complex time-dependent mechanisms involved in the kinetics of multiple cell types require a combination of experimental and mathematical modeling approaches. This study demonstrates such a combined approach by comparing normal neurogenesis with that altered by diet-induced accelerated aging in adult zebrafish.

University-based physical literacy programming for children: Canadian community stakeholders' recommendations.

'Physical literacy' (PL) education-that is, teaching foundational skills, attitudes, behaviors and knowledge about lifelong involvements in physical activities, is an important aspect for health promotion among children. Universities have been playing a critical role by teaching future PL professionals. Additionally, various universities have offered university-based PL programming for neighborhood children as a way of public health promotion service and community engagement. However, this additional role of universities and the ways of promoting the quality of this type of health promotion service programming have not been investigated in the current research literature. Therefore, the purpose of this study was to identify the practicable strategies to enhance the quality of university-based PL programming for children from the perspectives of community stakeholders. Overall, 24 community stakeholders who held professional positions that are related to PL education participated in a 90-min focus group interview. This grounded theory study identified that university-based PL programming for children should be (i) inclusive, (ii) collaborative, (iii) welcoming and (iv) responsive. Practical suggestions and recommendations were also provided. This study has provided empirical knowledge to prioritize aspects for the future actions in planning and implementing university-based PL programming for children and informed for further cross-cultural comparisons amongst the perspectives of participants, university service providers and community stakeholders. The knowledge acquired from this research will also be translated to university service providers who operate similar type of health promotion service programming to the public.

Letter to the Editor: The development of knights cabin cancer retreats: a community program to engage cancer survivors' proactive health behaviors

Purpose: Cancer survivors often lack the knowledge and skills to return to positive health behaviors following a cancer diagnosis. The use of retreats may be an ideal environment for cancer survivors to learn about health behaviours while receiving social support from other survivors. Methods: Knights Cabin Cancer Retreats was created as a charitable organization in 2014 and is at no cost to participants or their supporters. Elements of the retreat include guided hikes, yoga, classes on nutrition, stress, mindfulness and sleep management techniques, all with a focus on the evidence based theories of behavioral change. Results: Ten retreats have been hosted across Canada to date with 137 cancer survivors and their supporters. Survivors reported that their top learning outcomes from the retreat were physical activity/nutrition and behavioral change/habit development. Conclusion: Knight's Cabin Cancer retreats are unique in their programming with a format of health education that allows for emotional support and engagement with other cancer survivors in a therapeutically natural environment.

Exploring Associations of Sedentary Behavior and Physical Activity with Quality of Life in Young Adult Cancer Survivors.

PURPOSE: To explore sedentary behavior, physical activity (PA), and quality of life (QoL) in young adult cancer survivors (YACS), a population that is underrepresented in the literature. METHODS: YACS 18-44 years of age, recruited through social media and cancer support group websites (e.g., Young Adult Cancer Canada), completed an online survey, which assessed sedentary behavior, PA, and QoL using validated measures (i.e., The SIT-Q, Leisure Score Index [LSI], Short Form-36 Health Survey [SF-36], and Functional Assessment of Cancer Therapy: General [FACT-G]). RESULTS: Results indicated that YACS accumulated an average of 13.0 (SD = 4.6) hours/day of total sedentary time and reported watching TV for an average of 2.3 (SD = 1.9) hours/day. For PA, participants reported a mean of 113 minutes/week of moderate-to-vigorous PA (SD = 132) and low levels of resistance exercise (M = 26 minutes/week, SD = 58). Almost a third of the participants met the public health-recommended PA guidelines, and moderate-to-vigorous PA was positively correlated with the physical component score (PCS) (r = 0.3, p < 0.01) of the SF-36. Regression analyses showed that moderate-to-vigorous PA significantly predicted the PCS [F(1, 93) = 10.6, p < 0.01, R2 = 0.1], whereas napping and TV viewing time were inversely associated with the PCS [F(2, 93) = 6.9, p < 0.01, R2 = 0.1]. CONCLUSION: Total sedentary behavior, while considerable, was not related to QoL in YACS. However, TV watching was negatively associated with QoL, suggesting the importance of measuring TV watching and other domain-specific behaviors in studies on sedentary behavior. PA levels were also associated with QoL levels in YACS.

Evaluation of the accuracy and availability of cancer-related physical activity and sedentary behaviour information on English-language websites.

PURPOSE: To assess the quality and accuracy of cancer-related physical activity (PA) and sedentary behaviour (SB) information provided on major cancer websites from English-speaking countries. DESIGN: The study used a cross-sectional design. SAMPLE: A list of major cancer websites (N = 11) was generated from countries that speak English primarily (e.g., Canada, Australia). METHODS: These websites were assessed for quality and accuracy based on a detailed coding framework (e.g., PA guidelines, PA and cancer prevention). Frequencies and descriptive statistics were derived for website characteristics of interest. FINDINGS: All sites reviewed within this study offered PA information for cancer prevention and cancer survivorship. However, while 81% of the sites presented information for SB and cancer prevention, very little information was presented for SB and cancer survivorship, with only 18.2% of the information being offered. CONCLUSIONS: The quality and accuracy of cancer-related PA and SB information presented on leading cancer websites is variable. Further information is warranted in the areas of SB, resistance training, and behaviour change strategies. IMPLICATIONS: Websites have considerable value as knowledge translation tools and, therefore, presenting evidence-based information that is easy to understand may positively impact the health and behaviours of cancer populations, as well as the general population.

Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging.

Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

Evaluation of the use of shock index in identifying acute blood loss in healthy blood donor dogs.

OBJECTIVE: To determine if shock index (SI) would increase following blood donation and if it would be a more sensitive assessment of acute blood loss as compared with heart rate (HR), blood pressure, and plasma lactate. DESIGN: Prospective study. SETTING: University teaching hospital. ANIMALS: Twenty client-owned clinically normal dogs. INTERVENTIONS: Peripheral venous blood measurements and blood donation. MEASUREMENTS AND MAIN RESULTS: Data were collected at 3 time points: prior to donation (Tpre ), immediately after donation (T0 ), and 10 minutes following completion of donation (T10 ). HR and systolic blood pressure (SBP) were recorded and used to calculate SI at time points Tpre , T0 , and T10 . Packed cell volume (PCV), total plasma protein (TPP), and plasma lactate were evaluated from a peripheral venous blood sample at Tpre and T10. The mean SI was significantly increased at both time points following blood donation as compared to baseline (SIpre = 0.88 ± 0.19 vs SI0 = 1.17 ± 0.21 vs SI10 = 1.12 ± 0.25 (P = 0.0002 and 0.0003, respectively). Following blood donation, the mean SBP was significantly lower (SBPpre = 149 ± 24 mm Hg, SBP0 = 118 ± 20 mm Hg; P = 0.0001, SBP10 = 133 ± 21 mm Hg; P = 0.011). The mean HR was not significantly different at T0 but was significantly increased at T10 (HRpre = 128 ± 21/min, HR0 = 136 ± 25/min, P = 0.193; HR10 = 146 ± 29/min, P = 0.003). There was no significant difference in mean PCV (PCVpre = 50 ± 4%, PCV10 = 48 ± 4%, P = 0.08). The mean TPP and plasma lactate were significantly different following donation but still within the reference interval (TPPpre = 6.8 ± 0.4 g/dL, TPP10 = 6.4 ± 0.4 g/dL, P = 0.0014; Lacpre = 1.7 ± 0.7mmol/L, Lac10 = 1.9 ± 0.8 mmol/L, P = 0.04). A receiver operating characteristic (ROC) analysis comparing area under the curve (AUC) for SI, HR, and SBP at T0 and T10 compared to Tpre found that SI (AUC at T0 : 0.858, CI: 0.730, 0.984 AUC at T10 : 0.769 CI: 0.617, 0.921) was a better indicator of blood loss than SBP at both T0 (AUC 0.165, CI: 0.0384, 0.292, P < 0.0001) and T10 (AUC 0.288, CI: 0.124, 0.451, P < 0.001) and better than HR at T0 (AUC 0.574, CI: 0.392, 0.756, P < 0.001). An SI cut-off of 1.064 was 80% specific and 85% sensitive at T0 for detecting blood loss. CONCLUSIONS: An SI > 1.0 is a sensitive and specific tool for detecting acute small volume blood loss in healthy dogs.

The role of the built environment in a randomized controlled trial to increase physical activity among men with prostate cancer: the PROMOTE trial.

PURPOSE: The purpose of the study was to examine the association between the built environment and physical activity (PA) in prostate cancer survivors (PCS), as well as whether built environment factors (walkability, count of sports complexes) were effect modifiers of a PA intervention. METHODS: Our study included 165 PCS residing in Edmonton, Alberta, from the PROMOTE trial. The PROMOTE trial was a randomized controlled trial of a behaviour change intervention to increase PA and quality of life in PCS. In the PROMOTE trial, 423 PCS were randomly assigned to a standard physical activity recommendation, self-administered implementation intention, or telephone-assisted implementation intention group. PA and quality of life outcomes were assessed at baseline, 1, and 3 months. To explore the role of the built environment, this study examined walkability and count of sport complexes. RESULTS: Linear regression analyses revealed that the self-administered intervention group had an increase in self-reported PA minutes/week (ß = 133.4, 95% CI = -18.9 to 285.6); however, none of the built environment variables were found to be significantly associated with PA. The logistic regression showed that the self-administered intervention group had a significantly greater likelihood of meeting the PA guidelines (OR = 2.1, 95% CI = 0.9 to 4.9), though no built environment variables were associated with PA levels. CONCLUSIONS: Our findings suggest that the built environment was not associated with PA and was not an effect modifier in a PA behaviour change intervention for PCS. Further research is needed before clear conclusions can be generated ( ClinicalTrials.gov number NCT01410656).